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Int J Cancer. 2009 Mar 15;124(6):1483-9. doi: 10.1002/ijc.24094.

Spindle assembly checkpoint and p53 deficiencies cooperate for tumorigenesis in mice.

Author information

1
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Abstract

The spindle assembly checkpoint (SAC) guards against chromosomal missegregation during mitosis. To investigate the role of SAC in tumor development, mice heterozygously knocked out for the mitotic arrest deficient (Mad) genes Mad1 and/or Mad2 were mated with p53(+/) (-) mice. Increased tumor frequencies were reproducibly observed in Mad2(+/) (-)p53(+/) (-) (88.2%) and Mad1(+/) (-)Mad2(+/) (-)p53(+/) (-) (95.0%) mice compared with p53(+/) (-) (66.7%) mice. Moreover, 53% of Mad2(+/) (-)p53(+/) (-) mice developed lymphomas compared with 11% of p53(+/) (-) mice. By examining chromosome content, increased loss in diploidy was seen in cells from Mad2(+/) (-)p53(+/) (-) versus p53(+/) (-) mice, correlating loss of SAC function, in a p53(+/) (-) context, with increased aneuploidy and tumorigenesis. The findings here provide evidence for a cooperative role of Mad1/Mad2 and p53 genes in preventing tumor development.

PMID:
19065665
PMCID:
PMC2706662
DOI:
10.1002/ijc.24094
[Indexed for MEDLINE]
Free PMC Article

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